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Ze Zhang,1 Haotian Zhao,2 Zhiyang Zhang,1 Lijing Jia,1 Ling Long,1 You Fu,1 Quansheng Du1 1Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Ultrasound, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Quansheng Du, Department of Intensive Care Unit, Hebei General Hospital, Shijiazhuang, 050000, Hebei, People’s Republic of China, Email duquansheng@hebmu.edu.cnBackground: Acute respiratory distress syndrome (ARDS) is a severe form of organ dysfunction and a common postoperative complication. This study aims to develop a predictive model for ARDS in postoperative patients with gastrointestinal perforation to facilitate early detection and effective prevention.Methods: In this single-center retrospective study, clinical data were collected from postoperative patients with gastrointestinal perforation admitted to the ICU in Hebei Provincial People’s Hospital from October 2017 to May 2024. Univariate analysis and multifactorial logistic regression analysis were used to determine the independent risk factors for developing ARDS. Nomograms were developed to show predictive models, and the discrimination, calibration, and clinical usefulness of the models were assessed using the C-index, calibration plots, and decision curve analysis (DCA).Results: Two hundred patients were ultimately included for analysis. In the development cohort, 38 (27.1%) of 140 patients developed ARDS, and in the internal validation cohort, 13 (21.7%) of 60 patients developed ARDS. The multivariate logistic regression analysis revealed the site of perforation (OR = 0.164, P = 0.006), the duration of surgery (OR = 0.986, P = 0.008), BMI (OR = 1.197, P = 0.015), SOFA (OR = 1.443, P = 0.001), lactate (OR = 1.500, P = 0.017), and albumin (OR = 0.889, P = 0.007) as the independent risk factors for ARDS development. The area under the curve (AUC) was 0.921 (95% CI: 0.869, 0.973) for the development cohort and 0.894 (95% CI: 0.809, 0.978) for the validation cohort. The calibration curve and decision curve analysis (DCA) demonstrate that the nomogram possesses good predictive value and clinical practicability.Conclusion: Our research introduced a nomogram that integrates six independent risk factors, facilitating the precise prediction of ARDS risk in postoperative patients following gastrointestinal perforation.Keywords: gastrointestinal perforation, acute respiratory distress syndrome, prediction model, nomogram

Hongxing Dang,1– 3 Shaojun Li,1,3,4 Jing Li,1– 3 Li Long5 1Department of Pediatric Intensive Care Unit, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Ministry of Education Key Laboratory of Child Development and Disorders of China, Chongqing, People’s Republic of China; 3China National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China; 4Department of Emergency Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Health Management Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Li Long; Jing Li, Email longli@hospital.cqmu.edu.cn; lijingwangyi@126.comObjective: The second year of undergraduate medical education is a critical phase transitioning from basic medical knowledge to specialized learning, requiring strong critical thinking abilities. Pediatric diseases, with their unique characteristics, demand active critical thinking from pediatricians. This study aims to investigate and analyze the critical thinking dispositions of second-year pediatric medical students, identify influencing factors, and propose recommendations for improving teaching methods.Methods: This cross-sectional study employed the Chinese version of the California Critical Thinking Disposition Inventory (CTDI-CV) and conducted an online survey among 240 second-year pediatric medical students at Chongqing Medical University, Chongqing, China. The study described the overall CTDI-CV scores and sub-dimension scores (mean ± standard deviation) and analyzed the distribution of critical thinking dispositions using t-tests and trend analysis.Results: A total of 229 students (95.4%) completed the survey, with 58.95% being female. The overall mean critical thinking score was 287.96 ± 39.09, and 139 students (60.70%) exhibited positive or highly positive critical thinking dispositions. Rural students scored lower than non-rural students (t = − 2.773, P = 0.0069), while only children scored higher than non-only children (t = 2.659, P = 0.0086). Higher high school academic ranking was associated with higher scores (H = 23.85, P < 0.001). Students whose parents had a bachelor’s degree or higher scored significantly better (t = 2.373, P = 0.0188). Interest in pediatrics was linked to higher scores (H = 15.36, P = 0.0015). Positive correlations were found between analyticity, inquisitiveness, and self-confidence (r ≥ 0.75).Conclusion: Second-year pediatric medical students in China generally display strong critical thinking abilities. Factors such as family background, academic performance, parental education level, and interest in pediatrics significantly influence these abilities. Pediatric educators should account for these individual differences to better enhance critical thinking development in students and improve teaching strategies accordingly.Keywords: Critical Thinking Disposition, Medical Education, Pediatrics, Undergraduates

Kun Wang,1 Wei Zhu,2 Wei Huang,3 Kangkang Huang,1 Huidan Luo,1 Lu Long,1 Bin Yi1 1Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 3Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Bin Yi, Tel +86-13707495781, Email xyyibin@163.comObjective: Ubiquitination is an important post-translational modification. However, the significance of the TRIM family of E3 ubiquitin ligases in head and neck squamous cell carcinoma (HNSCC) has not been determined. In this study, the roles of TRIM E3 ubiquitin ligases in lymphovascular invasion in head and neck squamous cell carcinoma (HNSCC) were evaluated.Materials and Methods: TRIM expression and related parameters were obtained from UbiBrowser2.0, UALCAN, TIMER, TISIDB, LinkedOmics, STRING, and GeneMANIA databases. Immunohistochemistry was used to confirm their expression.Results: TRIM2, TRIM11, TRIM28, and TRIM56 were upregulated in HNSCC with lymphovascular invasion. TRIM expression was strongly associated with immune infiltration, including key treatment targets, like PD-1 and CTL4. Co-expressed genes and possible ubiquitination substrates included tumor-related factors. The TRIMs had predicted roles in ubiquitination-related pathways and vital signaling pathways, eg, MAPK, PI3K-Akt, and JAK-STAT signaling pathways.Conclusion: Ubiquitination mediated by four TRIMs might be involved in the regulation of tumor immunity, laying the foundation for future studies of the roles of the TRIM family on the prediction and personalized medicine in HNSCC. The four TRIMs might exert oncogenic effects by promoting lymphovascular invasion in HNSCC.Keywords: ubiquitination, TRIM, head and neck squamous cell carcinoma, bioinformatic analysis, lymphovascular invasion

Liying Long,1,2,&ast; Haiyan Peng,1,2,&ast; Xi Chen,1,2 Fei Wang,1,2 Wenjie Long,1,2 Ming Cheng,1,2 Jing Ma1,2 1Department of Psychiatry, The School of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Psychiatry, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), Changsha, Hunan, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Ma, Department of Psychiatry, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), No. 427, Section 3, Furong Middle Road, Yuhua District, Changsha, Hunan, 410007, People’s Republic of China, Tel/Fax +86-731-85232224, Email 853168933@qq.comBackground and Purpose: This study aimed to investigate the impact of implementing a low-lectin diet on gut microbiota composition and symptom amelioration in pediatric patients diagnosed with Attention Deficit Hyperactivity Disorder (ADHD).Methods: A total of 58 children (ages 7– 15 years), meeting the criteria for ADHD were recruited. In addition to standard medication treatment, participants in the experimental group with a low-lectin diet, while those in the control group received standard medication treatment alone. Clinical outcomes were assessed through evaluations conducted by physicians and teachers, implementation of the Conners Parent Rating Scales, and analysis of gut microbiota composition.Results: The results revealed significant improvements in symptom reduction and attention allocation rate within the experimental group, surpassing those observed in the control group. Specifically, the experimental group exhibited lower physician ratings, teacher ratings, and attention allocation rate compared to the control group. Moreover, analysis of gut microbiota composition identified notable distinctions between the two groups.Conclusion: These findings provide compelling evidence and valuable guidance supporting the integration of a low-lectin diet as an adjunctive intervention for managing ADHD.Keywords: ADHD, gut microbiota, low-lectin diet, integrative intervention, children

Dong-Mei Cai,1,&ast; Fan-Biao Mei,1,&ast; Chao-Jun Zhang,1 San-Chun An,1 Rui-Bo Lv,1 Guan-Hua Ren,1 Chan-Chan Xiao,1 Long Long,1,2 Tian-Ren Huang,1,2 Wei Deng1,2 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Deng; Tianren Huang, Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71, Hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email dengwei@gxmu.edu.cn; tianrenhuang@sina.comBackground: Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated.Methods: We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC. The relationships between MC-LR and both redox status and liver diseases in 177 local residents were analyzed. The hepatoma cell line HepG2 transfected with C-terminal truncated hepatitis B virus X gene (Ct-HBX) were treated with MC-LR. Reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were measured. Cell proliferation, migration, invasion, and apoptosis were assessed with cell activity assays, scratch and transwell assays, and flow cytometry, respectively. The mRNA and protein expression-related redox status genes were analyzed with qPCR and Western blotting.Results: The average concentration of MC-LR in well water, river water and reservoir water were 57.55 ng/L, 76.74 ng/L and 132.86 ng/L respectively, and the differences were statistically significant (P < 0.05). The MC-LR levels in drinking water were correlated with liver health status, including hepatitis, clonorchiasis, glutamic pyruvic transaminase abnormalities and hepatitis B surface antigen carriage (all P values < 0.05). The serum MDA increased in subjects who drank reservoir water and were infected with HBV (P < 0.05). In the cell experiment, ROS increased when Ct-HBX-transfected HepG2 cells were treated with MC-LR, followed by a decrease in SOD and GSH and an increase in MDA. MC-LR combined with Ct-HBX promoted the proliferation, migration and invasion of HepG2 cells, upregulated the mRNA and protein expression of MAOA gene, and downregulated UCP2 and GPX1 genes.Conclusion: MC-LR and HBV may synergistically affect redox status and play an important role in hepatocarcinoma genesis.Keywords: hepatocellular carcinoma, microcystins-LR, hepatitis B virus X gene, redox balance

In response to the difficulties posed by the resolution, line edge roughness, sensitivity (RLS) trade-off to traditional chemically amplified resist (CAR) systems used for extreme ultraviolet lithography, a number of novel resist technologies have been proposed. In this paper, the effect of quencher loading on three resist technologies is analyzed via an error propagation-based resist simulator. In order of increasing novelty as well as complexity, they are: Conventional CAR with quencher, CAR with photodecomposable base, and PSCAR 2.0, a CAR system with photodecomposable base as well as an EUV-activated UV-sensitive resist component. Simulation finds the more complicated resist systems trade in an increase in resist stochastics for improved deprotection slopes, yielding a net benefit in terms of line width roughness.

Tao Wang,1,2,&ast; Fa Long,1,&ast; Zhihui Huang,1 Liang Long,1 Wenting Huang,1 Siyu Hu,1 Fengbo Hu,1 Peng Fu,1 Jingfan Gan,1 Hongbo Dong,1 Guomei Yan1 1University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fa Long, University of Chinese Academy of Sciences Shenzhen Hospital, No. 4253, Songbai Road, Guangming District, Shenzhen, 518106, People’s Republic of China, Tel +86-755-27461986, Email longfa_923@163.comObjective: To investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients.Methods: This work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response.Results: ACQ score (3.19± 1.14 vs 1.26± 0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53± 21.66 vs 66.19± 22.50), FEV1 (1.53± 0.74 vs 1.93± 0.82), and forced vital capacity (FVC) (2.49± 0.86 vs 2.92± 0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions.Conclusion: Main bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.Keywords: refractory asthma, bronchial thermoplasty, activation, response, correlation

Yunxiao Zhong,1,&ast; Xiaodong Cai,2,&ast; Li Ding,3,&ast; Jinchi Liao,1 Xu Liu,1 Yiying Huang,1 Xiaohong Chen,1 Ling Long1 1Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510600, People’s Republic of China; 2Department of Neurology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510655, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Long; Xiaohong ChenDepartment of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510600, People’s Republic of China, Tel +86-20-85253275Email longl3@mail.sysu.edu.cn; chenxh5@mail.sysu.edu.cnObjective: Parkinson’s disease (PD) is associated with dysregulated neural cell death, such as pyroptosis, but its regulatory mechanisms are poorly understood. This study investigated roles of nuclear factor E2-related factor 2 (Nrf2) in regulating pyroptosis and PD development.Methods: Cellular and rat PD models established by 6-OHDA exposure were subjected to Nrf2 overexpression. Neurobehavioral functions were assessed by the traction test, Morris Water Maze, and open field test. Cell proliferation was analyzed by MTS assay, while flow cytometry was applied to quantify levels of reactive oxygen species (ROS) and apoptosis. Nissl bodies in rat brains were detected by Nissl staining, and cell apoptosis in brain tissues was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Differential expression of lncRNA and mRNA was characterized by deep sequencing.Results: A cellular PD model was successfully established by inducing PC12 cell differentiation with nerve growth factor-β and exposing differentiated cells to 6-OHDA. Cells exhibited significantly increased ROS levels, enhanced pyroptosis, and inhibited Nrf2 phosphorylation. The rat PD model exhibited impaired muscle strength, increased pyroptosis, and repressed Nrf2 phosphorylation. Nrf2 overexpression effectively repressed pyroptosis in both cellular and rat PD models. Marked alterations of lncRNA and mRNA profiles were induced by Nrf2 overexpression in the cellular PD model, which involved multiple signaling pathways. Silencing of the lncRNA AABR07032261.5 significantly promoted pyroptosis in the cellular PD model.Conclusion: Nrf2 suppressed PD pathogenesis in cellular and animal models by promoting AABR07032261.5, which repressed pyroptosis.Keywords: Nrf2, lncRNAs, AABR07032261.5, oxidative stress, pyroptosis, Parkinson’s disease

Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.

Hongfang Zeng,1– 3,&ast; Xiaoli Li,1– 3,&ast; Duanfang Zhou,1– 3 Ning Wang,4 Xiaoping Yu,1– 3 Liangyuan Long,1,3 Hao Cheng,5,6 Shuyu Zhou,5 Zhengze Shen,7 Weiying Zhou1– 3 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Drug Metabolism, Chongqing, People’s Republic of China; 3Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 4West China Biopharm Research Institute, West China Hospital, Chengdu, Sichuan Province, 610041, People’s Republic of China; 5China Company 18th, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 6Department of Pharmacy, Medical Security Center, the 925 Hospital, Joint Logistic Support Force, Guiyang, Guizhou Province, 550005, People’s Republic of China; 7Department of Pharmacy, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiying ZhouDepartment of Pharmacology, College of Pharmacy, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel/Fax +86 23 684 85161Email wyzhou0118@163.comPurpose: To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice.Materials and Methods: Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses.Results: Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice.Conclusion: The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.Keywords: type 2 diabetes mellitus, T2DM, Traditional Chinese medicine, TCM, TXNIP, anti-inflammatory

The gut microbiota is a complex ecosystem composed of many bacteria and their metabolites.It plays an irreplaceable role in human digestion, nutrient absorption, energy supply, fat metabolism, immune regulation, and many other aspects. Exploring the structure and function of the gut microbiota, as well as their key genes and metabolites, will enable the early diagnosis and auxiliary diagnosis of diseases, new treatment methods, better effects of drug treatments, and better guidance in the use of antibiotics. The identification of gut microbiota plays an important role in clinical diagnosis and treatment, as well as in drug research and development. Therefore, it is necessary to conduct a comprehensive review of this rapidly evolving topic. Traditional identification methods cannot comprehensively capture the diversity of gut microbiota. Currently, with the rapid development of molecular biology, the classification and identification methods for gut microbiota have evolved from the initial phenotypic and chemical identification to identification at the molecular level. This review integrates the main methods of gut microbiota identification and evaluates their application. We pay special attention to the research progress on molecular biological methods and focus on the application of high-throughput sequencing technology in the identification of gut microbiota. This revolutionary method for intestinal flora identification heralds a new chapter in our understanding of the microbial world. [ABSTRACT FROM AUTHOR]

Xiaojiao Zhou, Liling Long, Zhiqing Mo, Yajuan Li Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of ChinaCorrespondence: Liling LongDepartment of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of ChinaTel +86 13807712604Email Cjr.longliling@vip.163.comBackground: To evaluate the predictive value of the OATP1B3 expression in hepatocellular carcinoma (HCC) for the gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) uptake and the signal intensity (SI) in the hepatobiliary (HB) phase.Methods: In this retrospective study, we analyzed 69 liver nodules of 64 patients who underwent Gd-EOB-DTPA enhancement magnetic resonance imaging (MRI) before operation. Based on the SI in the HB phase, the patients were categorized into the hypointense HCC and iso- or hyperintense HCC groups. The OATP1B3 expression was detected by polymerase chain reaction (PCR) and immunohistochemistry. The differences between the expression of OATP1B3 and Gd-EOB-DTPA enhanced magnetic resonance imaging between the two groups of hepatocellular carcinoma were compared. The relationship between the OATP1B3 expression and the SI and relative enhancement (RE) was analyzed.Results: The examined HCC nodules were 59 hypointense HCC and 10 iso- or hyperintense. The relative expressions of OATP1B3, HB-phase signal, and the RE of the HB phase in iso- or hyperintense were significantly higher than those of the hypointense HCC, while the RE of the HB phase increased with an increase in the OATP1B3 expression (P < 0.05).Conclusion: The OATP1B3 expression in HCC can predict the uptake of Gd-EOB-DTPA and the SI of the HB phase. We believe that the evaluation of OATP1B3 expression will facilitate the comprehension of imaging performance of HCC in Gd-EOB-DTPA-enhanced MRI.Keywords: carcinoma, hepatocellular, gadolinium ethoxybenzyl DTPA, magnetic resonance imaging, OATP1B3

Langzi Tan, Yayu Chen, Wenyue Wu, Chaorong Liu, Yujiao Fu, Jialinzi He, Min Zhang, Ge Wang, Kangrun Wang, Hongyu Long, Wenbiao Xiao, Bo Xiao, Lili Long Department of Neurology, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Lili LongDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaTel +86 0731 84328888Fax +86 0731 84327332Email longlili1982@126.comPurpose: Patients with temporal lobe epilepsy (TLE) are at high risk of cognitive impairment. In addition to persistent seizures and antiepileptic drugs (AEDs), genetic factors also play an important role in the progression of cognitive deficits in TLE patients. Defining a cognitive endophenotype for TLE can provide information on the risk of cognitive impairment in patients. This study investigated the cognitive endophenotype of TLE by comparing neuropsychological function between patients with TLE, their unaffected siblings, and healthy control subjects.Patients and Methods: A total of 46 patients with TLE, 26 siblings, and 33 control subjects were recruited. Cognitive function (ie, general cognition, short- and long-term memory, attention, visuospatial and executive functions, and working memory) was assessed with a battery of neuropsychological tests. Differences between groups were evaluated by analysis of covariance, with age and years of education as covariates. The Kruskal–Wallis test was used to evaluate data that did not satisfy the homogeneity of variance assumption. Pairwise comparisons were adjusted by Bonferroni correction, with a significance threshold of P< 0.05.Results: Patients with TLE showed deficits in the information test (P< 0.001), arithmetic test (P=0.003), digit symbol substitution test (P=0.001), block design test (BDT; P=0.005), and backward digit span test (P=0.001) and took a longer time to complete the Hayling test Part A (P=0.011) compared to controls. Left TLE patients tended to have worse executive function test scores than right TLE patients. The siblings of TLE patients showed deficits in the BDT (P=0.006, Bonferroni-corrected) relative to controls.Conclusion: Patients with TLE exhibit cognitive impairment. Executive function is worse in patients with left TLE than in those with right TLE. Siblings show impaired visuospatial function relative to controls. Thus, cognitive deficits in TLE patients have a genetic component and are independent of seizures or AED use.Keywords: temporal lobe epilepsy, cognitive impairment, endophenotype

Aidi Zhang,1 Lianhong Wang,2 Lu Long,1 Jin Yan,1,3 Chun Liu,4 Sucui Zhu,1 Xiaowan Wang5 1Nursing Department, Third Xiangya Hospital of Central South University, Changsha 410013, People’s Republic of China; 2The First Affiliated Hospital of Zunyi Medical University, Zunyi 563003, People’s Republic of China; 3Xiang Ya Nursing School of Central South University, Changsha 410013, People’s Republic of China; 4Respiratory Department, Third Xiangya Hospital of Central South University, Changsha 410013, People’s Republic of China; 5Center for Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of ChinaCorrespondence: Jin Yan Email yanjin0163@163.comObjective: Hospital-outreach pulmonary rehabilitation (PR) can improve health status and reduce health-care utilization by patients with chronic obstructive pulmonary disease (COPD). However, its long-term effects and costs versus benefits are still not clear. This study was conducted to develop, deliver, and evaluate the effects and monetary savings of a hospital-outreach PR program for patients with COPD.Methods: A randomized controlled trial was conducted. Patients with COPD (n=208) were randomly assigned to the hospital-outreach PR program (treatment) or treatment as usual (control). The treatment group received a 3-month intensive intervention, including supervised physical exercise, smoking cessation, self-management education, and psychosocial support, followed by long-term access to a nurse through telephone follow-up and home visits up to 24 months. The control group received routine care, including discharge education and a self-management education brochure. Main outcomes were collected at 3, 6, 12, and 24 -months postrandomization. Primary outcomes included health-care utilization (ie, readmission rates, times, and days, and emergency department visits) and medical costs. Secondary outcomes included lung function (ie, FEV1, FEV1% predicted, FVC), dyspnea (mMCR), exercise capacity (6MWD), impact on quality of life (CAT), and self-management (CSMS).Results: At the end of 24 months, 85 (81.7%) in the treatment group and 89 (85.6%) in the control group had completed the whole program. Compared with the control group, patients in the treatment group had lower readmission rates, times, and days at 6 and 12 months and during 12– 24 months. Regarding costs during the 2 years, the program achieved CN¥ 3,655.94 medical savings per patient per year, and every ¥ 1 spent on the program led to ¥ 3.29 insavings. Patients in the treatment group achieved improvements in FEV1, FEV1% predicted, exercise capacity, and self-management. It also achieved relief of dyspnea symptoms and improvement in COPD’s impact on quality of life.Conclusion: The hospital-outreach PR program for patients with COPD achieved reductions in health-care utilization, monetary savings, and improvements in patient health outcomes. The effects of the program were sustained for at least 2 years.Trial Registration: This trial was registered at the Chinese Clinical Trial Registry (ChiCTR-TRC-14005108).Keywords: chronic obstructive pulmonary disease, savings, effects, hospital-outreach intervention, pulmonary rehabilitation

Lingli Long,1,2,* Minghua Lai,3,* Xuhong Mao,4 Jiahao Luo,3 Xin Yuan,2 Li-Ming Zhang,4 Zunfu Ke,5 Liqun Yang,3 David YB Deng1,2 1Department of Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People’s Republic of China; 2Department of Scientific Research Center and Orthopedic, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People’s Republic of China; 3Department of Polymer and Material Science, School of Chemistry, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Provincial Key Laboratory for High Performance Polymer-based Composites, Sun Yat-sen University, Guangzhou 510275, People’s Republic of China; 4Faculty of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People’s Republic of China; 5Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: David YB DengDepartment of Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People’s Republic of ChinaEmail dengyub@mail.sysu.edu.cnLiqun YangDepartment of Polymer and Material Science, School of Chemistry, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Provincial Key Laboratory for High Performance Polymer-based Composites, Sun Yat-sen University, Guangzhou 510275, People’s Republic of ChinaEmail yanglq@mail.sysu.edu.cnPurpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized.Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N’-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles.Results: They were observed as spherical nanoparticles in the size of 30–50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy.Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.Keywords: nanoparticle, insulin, human colon adenocarcinoma cell, small intestinal absorption efficacy

Long Long,1,* Xue Zhang,1,* Jian Bai,2,3 Yizhou Li,4 Xiaolong Wang,5 Yunfeng Zhou11Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 2Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, 430071, People’s Republic of China; 4Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 5Department of Urology, Research Lab/LIFE-Zentrum, University of Munich (LMU), München, Germany*These authors contributed equally to this workAbstract: Lung cancer is the most prevalent and deadly malignancy. Radiotherapy is a major treatment modality for lung cancer. Nevertheless, radioresistance poses a daunting challenge that largely limits the efficacy of radiotherapy. There is a pressing need for deciphering molecular mechanisms underlying radioresistance and elucidating novel therapeutic targets for individualized radiotherapy. MicroRNAs are categorized as small noncoding RNAs that modulate target-gene expression posttranscriptionally and are implicated in carcinogenesis and cancer resistance to treatment. Overwhelming evidence has unraveled that tissue-specific miRNAs are essential for regulation of the radiosensitivity in lung cancer cells through a complex interaction with multiple biological processes and radiation-induced pathways. Moreover, exosome-derived miRNAs are a novel horizon in lung cancer treatment in which exosomal miRNAs act as potential diagnostic and therapeutic biomarkers of radiotherapy. In the present review, we discuss the mediation of key biological processes and signaling pathways by tissue-specific miRNAs in lung cancer radiotherapy. Additionally, we provide new insight into the potential significance of exosomal miRNAs in radiation response. Lastly, we highlight miRNAs as promising predictors and therapeutic targets to tailor personalized lung cancer radiotherapy.Keywords: lung cancer, microRNAs, exosome, radioresistance, personalized radiotherapy

Nationwide, leaders in business and industry have increasingly acknowledged the importance of entrepreneurship. Several areas of the country showcase the importance of entrepreneurship such as Silicon Valley in California where a large number of start-up companies in science, technology, engineering and math (STEM) fields are located. To meet the needs of business and industry, institutions of higher education prepare students for future employment by offering rigorous and relevant coursework in areas such as entrepreneurship. Collegiate faculty and staff can use fundamental engineering courses to instill an entrepreneurial mindset -- a set of beliefs, attitudes, and behaviors that drive innovation -- in their students. This paper will explore an open-ended team project within a freshman-level engineering graphics course in which instructors encourage an entrepreneurial mindset in students. The goal of the course project is to develop engineering students' critical thinking and innovation skills while preparing them for their future professions. An end-of-semester course-wide poster competition allowed students to practice teamwork as well as innovative thinking and communication skills.

PurposePreoperative cognitive impairment is associated with the development of postoperative delirium, a common and consequential complication of major surgery in older patients. Screening for cognitive impairment should become a routine part of the preoperative evaluation of older patients; however, its implementation is hampered by limited clinical time and resources. The objective of this review was to identify cognitive screening tools that could be easily incorporated into the evaluation of older patients before major surgery.Search strategyUsing strict inclusion and exclusion criteria, we searched PubMed over a 15-year period for short and simple cognitive screening tools. In addition, we reviewed studies that examined these cognitive screening tools in a perioperative environment. SEARCH RESULTS: We identified six cognitive screening tools that could each be administered in 2.5 min or less. Among the tools, sensitivity for cognitive impairment ranged from 79-99%, while specificity ranged from 70-98%. Only one (Mini-Cog) of the six tools we identified had been tested in a perioperative environment.ConclusionsIncorporating a cognitive screening assessment into the preoperative evaluation of older patients is feasible. More research is needed to validate cognitive screening tools in the perioperative setting.

Yang Yao,1,* Jie Su,1,* Lei Zhao,2 Na Luo,3 Lihui Long,4 Xingmei Zhu5 1Department of Central Laboratory, The First Affiliated Hospital, Xi’an Medical University, Xi’an, Shaanxi 710077, PR China; 2Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; 3Department of Clinical Medicine (Four-Year Program) of Grade 2014, Xi’an Medical University, Xi’an, Shaanxi 710021, PR China; 4Department of Pharmacy, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi 710077, PR China; 5Department of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China *These authors contributed equally to this work Objective: NIMA-related kinase 2 (NEK2) has been reported to be overexpressed in various types of cancer and correlated with poor prognosis. The role(s) of NEK2 in cancer, however, is still uncertain. The aim of this study was to evaluate the prognostic value of NEK2 in human tumors. Methods: A comprehensive literature search was performed for PubMed, Embase, Web of Science, and CNKI databases, and eligible studies were included based on the inclusion and exclusion criteria. A meta-analysis of the included studies was then carried out. Results: Fifteen studies with 3,280 cancer patients were included in the present meta-analysis. All publications were of moderate to high quality, and had no significant heterogeneity (I2=46%, P=0.03) or publication bias was discovered. The results showed that a high NEK2 level was associated with shorter overall survival (OS) in patients with various types of cancers (pooled HR=1.72, 95% CI 1.49–2.00, P

Xiaorong Zhou,1 Manli Xu,2 Yonghong Guo,1 Ling Ye,1 Limin Long,1 Haiqin Wang,1 Pan Tan,1 Meili Xu1 1Department of Gerontology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; 2Department of Basic Medicine, Guizhou College of Health Professions, Tongren, Guizhou, 554300, China Background: miRNAs are potential regulators of genes in many cancers. Here, we confirmed that the expression of miR-588 decreased in gastric cancer (GC) tissues and cells.Materials and methods: Sixty-seven GC tissues along with noncancerous tissues adjacent to them were included in the study. Quantitative real-time reverse transcription-PCR study was done to quantify the expression levels of mature miRNA. The expression of proteins was determined by Western blot and transwell chamber assay for invasion and migration studies. Immunohistochemical analysis and luciferase assay were done for evaluating the expression of epithelial–mesenchymal transition (EMT) markers and activity of EIF5A2, respectively. In vivo metastatic assay was done by injecting MGC-803 cells into nude mice.Results: In the 5-year predicted survival study of GC patients included in the study, we found that miR-588 acted as a specific prognostic marker. Overexpression of miR-588 resulted in suppression of cell invasion, migration and progression of EMT, whereas suppression of miR-588 inverted the effects in both in vivo and in vitro experiments. miR-588 retained EIF5A2 by directly binding to the 3´-UTR. EIF5A2 was overexpressed in GC tissue samples, and the expression of miR-588 was inversely correlated to the levels of EIF5A2. The impact of miR-588 on invasion, migration and progression of EMT may be partially due to miR-588–mediated alterations of EiF5A2.Conclusion: Overall, the findings of the study suggest that miR-588 acts as a tumor suppressor by regulating the invasion, migration and EMT via EIF5A2 pathway, hence presenting miR-588 as a prognostic marker as well as a therapeutic target for GC. Keywords: miR-588, gastric cancer, EIF5A2, EMT

Tao Zhang,1 Fang Tian,2 Lin Long,1 Jianbo Liu,3 Xiaochun Wu4 1Department of Clinical Laboratory, Zaozhuang Municipal Center for Disease Control and Prevention, Zaozhuang, China; 2Department of Clinical Laboratory, Zaozhuang Municipal Maternal and Child Health Hospital, Zaozhuang, China; 3College of Opto-electronic Engineering, Zaozhuang University, Zaozhuang, China; 4CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing, China Background: As nanotechnology advances rapidly, the nanozymes which could replace protein enzymes in bioanalytical assays bring a new opportunity to the development of simple and sensitive diagnostic tools. Purpose: Antibody-conjugated Au-Pt core/shell nanorods (Au@Pt NRs) have been used for nanozyme probes for diagnosis of rubella virus. Au@Pt NRs, prepared by Au nanorod-mediated growth, exhibit peroxidase-like activities and could serve as an inexpensive replacement for horseradish peroxidase (HRP) in conjugation of antigen. Method: Using a capture enzyme-linked immunosorbant assay for the determination of rubella virus. Results: Compared with antibody-conjugated HRP, the antigen-conjugated Au@Pt NRs are more stable and more robust, but less expensive. Based on the enhanced catalytic properties of this nanozyme probe, it was found that the antigen-conjugated Au@Pt NRs-based enzyme-linked immunosorbant assay exhibited good sensitivity. Conclusion: Our results indicate that these antigen-conjugated Au@Pt NRs represent a suitable nanozyme probe for future clinical applications under various conditions. Keywords: gold nanorods, nanozyme, antigen conjugation, rubella virus, diagnosis